Calibration system for use with lateral flow assay test strips

ABSTRACT

A method of adjusting a final signal value measured on a lateral flow assay test strip, by: identifying a pre-determined calibration method for the test strip, wherein the pre-determined calibration method corresponds to the manufacturing lot from which the test strip has been made; measuring signal values while performing a lateral flow assay reaction on a test strip; determining a final signal value; and adjusting the final signal value based upon the identified pre-selected calibration method for the test strip.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. patent application Ser.No. 11/175,554, filed Jul. 5, 2005, the disclosure of which isincorporated herein by reference.

TECHNICAL FIELD

The present invention relates to calibration systems for lateral flowassay test strip measurement systems.

BACKGROUND OF THE INVENTION

A common problem with lateral flow assay test strips is that differenttest strips tend to produce slightly different results. Unfortunately,no two test strips will perform exactly alike (i.e.: generate identicaltest result values) even if the test strips have the same amount ofreagent embedded therein, and even if they are both exposed to the sameamount of analyte. Such discrepancies in lateral flow assay test resultsmay be explained by differences in the physical properties of individualtest strips, and also by differences in the fluid flow path alongthrough different test strips. It would instead be desirable to providea system to reduce, or compensate for, such performance variances amongdifferent test strips.

The problem of different test strips exhibiting slightly different testresults becomes even more pronounced when the test strips aremanufactured from different lots of material. This is due to the factthat different test strip material lots tend to have slightly differentphysical properties. These material properties influence the spatialdistribution of reagents dried therein and, consequently, the efficiencywith which they are reconstituted into flowing liquid.

Therefore, it would instead be desirable to provide a system thatcompensates for performance variances among different test strips both:(a) when the test strips are made from the same lot of material, and (b)when the test strips are made from different lots of material.

SUMMARY OF THE INVENTION

The present invention provides a calibration system that adjusts thefinal reflectance value measured on a test strip so as to compensate forvariations in results that are exhibited among a selection of similartest strips. In one preferred aspect, the calibration system adjusts thefinal measured reflectance value by comparison to test results exhibitedby other test strips that are all from the same manufacturing lot.

In another preferred aspect, the calibration system selects theparticular method that is used to perform the adjustment of finalreflectance. The selection of the method may involve identifying thepattern of reflectance profiles and associated parameter values uniquelycharacteristic of a given manufacturing lot of test strips. This systemof selecting the particular method to be used for adjusting the finalreflectance values of test strips from a particular manufacturing lot isparticularly advantageous in that test strips made from differentmanufacturing lots of material can each be calibrated differently.

In one preferred aspect, the present invention provides a method ofadjusting a final signal value measured on a lateral flow assay teststrip, by: identifying a pre-determined calibration method for the teststrip, wherein the pre-determined calibration method that is selected ischaracteristic of the manufacturing lot from which the test strip hasbeen made. Signal values are measured while performing a lateral flowassay reaction on a test strip; a final signal value is determined; andthe final signal value is then adjusted based upon the identifiedpre-selected calibration method that is used for the test strip.

For one particular manufacturing lot of test strips, the pre-determinedcalibration method for the test strip comprises: measuring signal valueswhile performing a lateral flow assay reaction on a test strip;determining a minimum signal value; determining an interim signal value,wherein the interim signal value is measured a pre-determined timeperiod after the minimum signal value is measured; determining a finalsignal value; and adjusting the final signal value based upon theinterim signal value. Optionally, more than one interim signal value maybe used, with each of the interim signal values being measured atdifferent times. Optionally as well, the predetermined time period maybe zero.

For another particular manufacturing lot of test strips, thepre-determined calibration method for the test strip comprises:measuring signal values while performing a lateral flow assay reactionon a test strip; determining a minimum signal value; determining thetime at which the minimum signal value is measured, determining a finalsignal value; and adjusting the final signal value based upon theminimum signal value and/or the time at which the minimum signal valueis measured.

For another particular manufacturing lot of test strips, thepre-determined calibration method for the test strip comprises:measuring signal values while performing a lateral flow assay reactionon a test strip, determining a total signal below a threshold value;determining a final signal value; and adjusting the final signal valuebased upon the total measured signal below the threshold value.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration of a pattern of reflectance profiles for arepresentative sample of lateral flow assay test strips from a firstmanufacturing lot of material.

FIG. 2 is an illustration of a pattern of reflectance profiles for arepresentative sample of lateral flow assay test strips from a secondmanufacturing lot of material.

FIG. 3 is an illustration of a pattern of reflectance profiles for arepresentative sample of lateral flow assay test strips from a third lotof manufacturing material.

FIG. 4 is an illustration of a pattern of reflectance profiles for arepresentative sample of lateral flow assay test strips from a fourthlot of manufacturing material.

FIG. 5 is an illustration of a pattern of reflectance profiles for arepresentative sample of lateral flow assay test strips from a fifth lotof manufacturing material.

DETAILED DESCRIPTION OF THE DRAWINGS

FIGS. 1 to 5 each illustrate a representative sample of reflectanceprofiles for a plurality of lateral flow assay test strips, showingdifferent patterns of kinetics in the test zones of the test strips,wherein: all of the test strips illustrated in FIG. 1 are made from afirst manufacturing lot of material; all of the test strips illustratedin FIG. 2 are made from a second manufacturing lot of material, etc.

The examples presented herebelow deal with test strip reflectanceprofiles. It is to be understood that the present invention is not solimited and that other optical properties including fluorescence orluminescence may be substituted. It is also to be understood that othernon-optical properties, including electrochemical signal values anddirect light transmission signal values may also instead be used withthe present calibration system.

In accordance with the present invention, a specific calibration systemis provided for different lots of test strips having the kineticproperties illustrated in each of FIGS. 1 to 5. For example, the teststrips from the lot illustrated in FIG. 1 are all calibrated by the onepreferred method. Similarly, each of the test strips illustrated in FIG.2 are all calibrated by another preferred method, and likewise for thetest strips illustrated in each of FIGS. 3 to 5. The particular methodsof test strip calibration and reflectance value adjustment for each ofthe test strip manufacturing lots in FIGS. 1 to 5 will be explainedfully below.

As stated above, the present invention also provides a system forselecting which specific method of test strip calibration is to be usedfor any given manufacturing lot of test strips. In accordance with thepresent invention, a determination is first made as to which kineticpattern (e.g.: as illustrated in each of FIGS. 1 to 5) is characteristicof the performance of the test strips in a particular manufacturing lot.Then, based on the performance of a representative sample of teststrips, the selected manufacturing lot of test strips is calibratedaccording to the kinetic pattern corresponding to FIG. 1, 2, 3, 4 or 5.For example, for the remaining test strips in the lot, a new test stripmay be identified as having the kinetic pattern shown in FIG. 1 (i.e.:the test strip is made from the manufacturing lot of FIG. 1). In thiscase, the adjustment of final reflectance is made according to themethod outlined with respect to FIG. 1. Similarly, if the selected teststrip was instead identified as having the kinetic pattern shown in FIG.2, (i.e.: being made from the manufacturing lot shown in FIG. 2); thecalibration of final reflectance is made according to the methodoutlined with respect to FIG. 2.

FIG. 1 illustrates reflectance kinetic profiles for a plurality of teststrips all from a first manufacturing lot. In accordance with thepresent invention, reflectance profiles are measured for arepresentative sample of test strips (illustrated here as #1 and #2)under as consistent test conditions as possible. (Such consistent testconditions entail the same amount of reagent in the test strips beingexposed to the same amount of analyte in a fluid sample.) From these twoextreme reflectance profiles (#1 and #2), a mean, median, expected or“ideal” exemplary test strip reflectance profile (#3) is determined. Itis to be understood that reflectance values from more than tworepresentative test strips (#1 and #2) are preferably used to determinethe mean test strip reflectance profile #3. Most typically, readingsfrom twenty five or more individual test strips (each falling betweenthe extreme profiles of #1 and #2) are used to determine the mean teststrip reflectance profile #3. Thus, it is only for clarity ofillustration that only two test strip reflectance profiles (#1 and #2),are shown. Moreover, for clarity of illustration, illustratedreflectance profiles #1 and #2 are the extreme profiles (with each ofthe other reflectance profiles for the twenty five or more test samplesfalling therebetween).

As can be seen, the measured reflectance profiles of each of the teststrips made from this first lot of material tend to vary from oneanother with a characteristic pattern, thereby producing a “family” ofcurves. Specifically, in this particular example, the final reflectancevalues F will tend to vary in relation to the minimum reflectance valuesM.

For example, the reflectance of test strip #1 reaches a minimum level M₁at time t_(min), and then reaches its final value F₁ at time t_(f).Similarly, the reflectance of test strip #2 reaches a minimum level M₂after the same elapsed time t_(min), and then reaches its final value F₂at the same elapsed time t_(f). Since the reflectance profiles of teststrips #1 and #2 both reach their minimum levels M₁ and M₂ at about thesame time t_(min), the mean reflectance profile of a nominal (i.e.:newly selected) test strip #3 will also reach its minimum level M₃ attime t_(min).

As can also be seen, for test strip #1, the difference between its finalreflectance value F₁ and the average or expected final reflectance valueF₃ will vary in relation to the difference between the minimumreflectance value M₁ and the mean minimum reflectance value M₃. Incertain exemplary cases, this relationship may be linear, but thepresent invention is not so limited.

Similarly, for test strip #2, the difference between its finalreflectance value F₂ and the average final reflectance value F₃ willvary in relation to the difference between the minimum reflectance valueM₂ and the mean minimum reflectance value M₃. In certain exemplarycases, this relationship may be linear, but again the present inventionis not so limited. A calibration equation with associated parametervalues may thus be defined for the manufacturing lot illustrated in FIG.1.

Therefore, variability in additional (i.e.: newly selected) test strips,made from the same manufacturing lot shown in FIG. 1, may be mitigatedby adjustment using the calibration information established as above forthis exemplary manufacturing lot of test strips, as follows. Thereflectance profile of an additional (i.e.: newly selected or “nominal”)test strip #4 is illustrated. Variation in the final reflectance valueof test strip #4 can be mitigated by simply measuring its minimumreflectance value M₄, at time t_(min), and adjusting its finalreflectance value F₄ downwardly (from F₄ to F₃) by an amountproportional to the difference between M₄ and M₃ according to thecalibration equation established for this exemplary manufacturing lot oftest strips. Note: if the minimum reflectance value of test strip #4does not occur near t_(min), an error message may be triggered.

FIG. 2 illustrates reflectance kinetic profiles for a plurality of teststrips from a second manufacturing lot of material. In accordance withthe present invention, reflectance profiles are measured for arepresentative sample of test strips (illustrated here as #1 and #2)under as consistent test conditions as possible. (As above, consistenttest conditions entail the same amount of reagent in the test stripsbeing exposed to the same amount of analyte in a fluid sample.) Fromthese two extreme reflectance profiles (#1 and #2), a mean, median,expected or “ideal” exemplary test strip reflectance profile (#3) isdetermined. It is to be understood that reflectance profiles from morethan two representative test strips (#1 and #2) are preferably used todetermine the mean test strip reflectance profile #3. Most typically,readings from twenty five or more individual test strips (each fallingbetween the extreme profiles of #1 and #2) are used to determine averagetest strip reflectance value #3. Thus, it is only for clarity ofillustration that only two test strip reflectance values (#1 and #2),are shown. Reflectance profile #3 thus represents a mean, or standard orexpected reflectance profile for a test strip that is made from the lotof material shown in FIG. 2. Moreover, for clarity of illustration,illustrated reflectance profiles #1 and #2 are the extreme profiles(with each of the other reflectance profiles for the twenty five or moretest samples falling therebetween).

As can be seen, the measured reflectance profiles of each of the teststrips made from this second lot of material tend to vary in the sameway from one another, within a characteristic pattern, thereby producinga “family” of curves. Specifically, in this particular example, thefinal reflectance values F will tend to vary in relation to an interimreflectance value I, with the minimum reflectance values, t_(n), allbeing essentially identical and all occurring at essentially the sametime t_(min).

For example, the reflectances of test strips #1 and #2 both reach thesame minimum level (i.e. M₁=M₂) at about the same time t_(min).Therefore, the reflectance of mean test strip #3 will also reach itsminimum level M₃ at about time t_(min). The reflectance of test strip #1then reaches its final value F₁ at time T_(f), and the reflectance oftest strip #2 also reaches its final value F₂ at time t_(f). As can beseen, the measured reflectances of test strips #1 and #2 will tend tovary most from one another when measured at an interim time periodt_(interim). Further, t_(interim) occurs at a time delay “Δt” aftert_(min) (i.e. at a time delay Δt after the measurement of minimumreflectances M₁ and M₂).

In the case of the measured test strip reflectance in the reflectanceprofile shown by test strip #1, the difference between the finalreflectance value F₁ and the average final reflectance value F₃ willvary in relation to the difference between the reflectance values I₁ andI₃ measured a pre-determined time delay “Δt” after t_(min) (i.e. at atime delay Δt after the minimum reflectance M₁ is measured). Forexample, the difference between the final reflectance value F₁ and theaverage final reflectance value F₃ is directly proportional to thedifference between the reflectance value measured at time t_(interim)between I₂ and I₃. In certain exemplary cases, this relationship may belinear, but the present invention is not so limited.

Similarly, in the case of the measured test strip reflectance profileshown by test strip #2, the difference between the final reflectancevalue F₂ and the mean final reflectance value F₃ will vary in relationto the difference between the reflectance values I₂ and I₃ measured apre-determined time delay “Δt” after t_(min) (i.e. at a time delay Δtafter the minimum reflectance M₂ is measured). For example, thedifference between the final reflectance value F₂ and the average finalreflectance value F₃ is directly proportional to the difference betweenthe reflectance values I₂ and I₃ measured at time t_(interim) between F₂and F₃. In certain exemplary cases, this relationship may be linear, butthe present invention is not so limited. As above, a calibrationequation with associated parameter values may thus be defined for themanufacturing lot illustrated in FIG. 2.

Therefore, variability in additional (i.e.: newly selected) test stripsmade from the same manufacturing lot shown in FIG. 2, may be mitigatedby adjustment using the calibration information established as above forthis exemplary manufacturing lot of test strips, as follows. Thereflectance profile of an additional (i.e.: newly selected) test strip#4 is illustrated. Variation in the final reflectance value of teststrip #4 can be mitigated by simply measuring its interim reflectancevalue I₄, and adjusting its final reflectance value F₄ downwardly (fromF₄ to F₃) by an amount proportional to the difference between I₄ and I₃according to the calibration equation established for this exemplarymanufacturing lot of test strips.

FIG. 3 illustrates reflectance kinetic profiles for a plurality of teststrips from a third manufacturing lot. In accordance with the presentinvention, reflectance profiles are measured for a representative sampleof test strips (illustrated as #1 and #2). From these two reflectanceprofiles (#1 and #2), a mean, median, expected or “ideal” exemplary teststrip reflectance profile (#3) is generated for the third lot ofmaterial. It is to be understood that reflectance profiles from morethan two representative test strips are preferably used to generate amean test strip reflectance profile #3. Most typically, readings fromtwenty five or more individual test strips (each falling between theillustrated extreme profiles of #1 and #2) are used to generate meantest strip reflectance profile #3. Thus, it is only for clarity ofillustration that only two test strip reflectance profiles (#1 and #2),are shown.

As can be seen, the measured reflectance profiles of each of the teststrips from this third lot of material tend to vary within acharacteristic pattern, thereby producing a “family” of curves. Morespecifically, in this particular example, the final reflectance values Fwill tend to vary in relation to the time at which the minimumreflectance value t_(min) is measured.

For example, the reflectance of test strip #1 reaches a minimum level M₁at time t_(min1), and then reaches its final value F₁ at time t_(f).Similarly, the reflectance of test strip #2 reaches its minimum level M₂at its own particular time t_(min2). As can be seen, the reflectance ofaverage test strip #3 will therefore also reach its minimum level M₃ atits own time t_(min3). As can be seen, the difference between the finalreflectance value F₁ or F₂ and the average final reflectance value F₃ isa function of the time at which t_(min1) or t_(min2) is reached.

Thus, in the case of test strips from the third lot (i.e.: the lotmeasured in FIG. 3) the final reflectance values can accurately beadjusted by simply determining when the minimum reflectance values aremeasured and applying the appropriate lot-specific calibration equationand associated parameter values.

Therefore, variability in additional (i.e.: newly selected) test stripsfrom the same manufacturing lot shown in FIG. 3, may be mitigated byadjustment using the calibration information established as above forthis exemplary manufacturing lot of test strips, as follows. Thereflectance profile of an additional (i.e.: newly selected) test strip#4 is illustrated. Variation in the final reflectance value of teststrip #4 can be mitigated by simply measuring the time t_(min4) at whichit reaches its minimum reflectance value M₄. As such, the finalreflectance value F₄ will be adjusted downwardly (from F₄ to F₃) by anamount proportional to the time difference between t_(min4) and t_(min3)according to the calibration equation established for this exemplarymanufacturing lot of test strips.

FIG. 4 illustrates reflectance kinetic profiles for a plurality of teststrips from a fourth manufacturing lot. In accordance with the presentinvention, reflectance profiles are measured for a representative sampleof test strips (illustrated as #1 and #2). From these two reflectanceprofiles (#1 and #2), a mean test strip reflectance profile (#3) isgenerated. It is to be understood that reflectance profiles from morethan two representative test strips are preferably used to generate anaverage test strip reflectance profile #3. Thus, it is only for clarityof illustration that only two test strip reflectance profiles (#1 and#2), are shown. Moreover, for clarity of illustration, illustratedreflectance profiles #1 and #2 are the extreme profiles (with each ofthe other reflectance profiles for the twenty five or more test samplesfalling therebetween).

As can be seen, the measured results of each of the test strips fromthis fourth lot of material tend to vary within a characteristicpattern, thereby producing a “family” of curves. More specifically, inthis particular example, the final reflectance values F will tend tovary in relation to both the minimum reflectance values and the time atwhich these minimum reflectance values are measured.

For example, the reflectance of test strip #1 reaches a minimum level M₁at time t_(min1) and then reaches its final value F₁ at time t_(f).Similarly, the reflectance of test strip #2 reaches its own minimumlevel M₂ at its own time t_(min2). Therefore, the reflectance of averagetest strip #3 will reach its minimum level M₃ at its own time t_(min3).

As can also be seen, the measured reflectances of test strips #1 and #2will tend to vary most from one another when measured at an interim timeperiod t_(interim). Further, t_(interim) occurs at various time delaysΔt_(n) after t_(min).

For example, I₁ occurs at t_(interim) (where t_(interim) is measured attime delay Δt₁ after minimum value M₁ has been measured). Similarly, I₂occurs at t_(interim) (where t_(interim) is measured at time delay Δt₂after minimum value M₂ has been measured). Therefore, I₃ will occur att_(interim) (where t_(interim) is measured at time delay Δt₃ afterminimum value M₃ has been measured).

Therefore, variability in additional (i.e.: newly selected) test stripsfrom the same manufacturing lot shown in FIG. 4, may be mitigated byadjustment using the calibration information established as above forthis exemplary manufacturing lot of test strips, as follows. Thereflectance profile of an additional (i.e.: newly added) test strip #4is illustrated. Variation in final reflectance value in test strip #4can be mitigated by adjusting the final reflectance value F₄ by simplydetermining both the minimum reflectance values, and the time at whichthe minimum reflectance values are measured, as follows.

For example, test strip #4 will be calibrated by first measuring theinterim value I₄ at time t_(interim) (measured at delay Δt₄ after itreaches its minimum reflectance value M₄). The length of delay Δt₄ isdetermined by the time t_(min4) at which M₄ is measured. As such, thefinal reflectance value F₄ will be adjusted upwardly (from F₄ to F₃) byan amount proportional to the difference between interim reflectancevalues I₄ and I₃ according to the calibration equation established forthis exemplary manufacturing lot of test strips.

In summary, each of FIGS. 1 to 4 illustrate different patterns ofreflectance kinetics, each being characteristic of a particularmanufacturing lot of test strips. In the case of the lot shown in FIG.1, adjustment of the final reflectance value F is made solely bycomparing minimum test values M. In the case of the lot shown in FIG. 2,adjustment of the final reflectance value F is made solely by comparinginterim reflectance values I (wherein the interim value I is measured apre-determined time period Δt after the minimum value M is detected). Inthe case of the lot shown in FIG. 3, adjustment of the final reflectancevalue F is made solely by comparing the time t_(min) at which theminimum test value M is detected. Lastly, in the case of the lot shownin FIG. 4, adjustment of the final reflectance value F is made bycomparing both the minimum test values M and the times t_(min) at whichthese minimum test values M are detected.

It is to be understood that the exemplary aspects of the preferredcalibration illustrated in FIGS. 1 to 4 are exemplary, and are notlimiting. For example, other suitable techniques may be used to generateor determine the exemplary mean reflectance profile (e.g.: reflectanceprofile #3) of an exemplary or nominal test strip from a particularmanufacturing lot.

Therefore, any suitable technique for determining an exemplaryreflectance profile (e.g.: reflectance profile #3) of a mean test stripmade from a particular manufacturing lot of material is encompassedwithin the scope of the present invention. Thus, calibration systemsincluding curve-fitting techniques, and techniques where measurementsare made at a number of different interim test points for each teststrip, are all encompassed within the scope of the present invention.The values taken at each of these different interim test points may beweighted equally, or they may be weighted differently from one anotherin computing the “ideal” or exemplary typical test strip reflectanceprofile #3 that is best representative for the particular manufacturinglot of test strips. In addition, systems that exhibit reflectanceprofile #3 and use medians instead of means are also encompassed withinthe scope of the present invention. Such an approach may be advantageousin that calculating medians tends to be more effective in reducing theeffects of outliers. Optionally, methods that take into account rates ofreflectance changes over time may also be used in calculating “ideal” orrepresentative exemplary test strip reflectance profiles #3.

FIG. 5 illustrates reflectance kinetic profiles for a plurality of teststrips from a fifth manufacturing lot. In accordance with the presentinvention, reflectance profiles are measured for a representative sampleof test strips (illustrated as #1 and #2). The final reflectance valueF₁ at time t_(f) for test strip #1 is determined. Then, the area (i.e.:the “total signal”) below a given reflectance value R and above line #1is determined. (See shaded area labeled INTEG 1.) Similarly, the finalreflectance value F₂ at time t_(f) for test strip #2 is determined.Then, the area (i.e.: the “total signal”) below final reflectance valueR and above line #2 is determined. (See shaded area labeled INTEG 2.)

From these two reflectance total signals (INTEG1 and INTEG 2), anaverage test strip reflectance total signal (INTEG3) is generated forthe lot of test strips illustrated in FIG. 5. It is to be understoodthat reflectance profiles from more than two representative test stripsare preferably used to generate an average test strip reflectanceprofile #3. Thus, it is only for clarity of illustration that only twotest strip reflectance profiles (#1 and #2), are shown. Note: in theexample shown in FIG. 5, the reflectance value R is the same as thefinal reflectance value F₃. This need not be true in all cases. Instead,other threshold reflectance values R may be used in accordance with thecalibration method illustrated in FIG. 5. Similar to the above describedFigs, reflectance profiles #1 and #2 are illustrated as extreme values.

In accordance with one aspect of the invention, the final reflectancevalue F₃ at time t_(f) for an average or ideal test strip #3 isdetermined. In addition, the area (i.e.: “total signal”) below finalreflectance value F₃ and above line #3 is also determined. (See shadedarea labeled INTEG 3.)

Therefore, in the case of newly selected test strips from the fifth lot(i.e.: the lot measured in FIG. 5) the final reflectance values canaccurately be adjusted by simply determining the total signal underreflectance value R for the particular newly selected test strip andapplying the appropriate lot-specific calibration equation andassociated parameter values.

For example, in the case of a new test strip #4 made from themanufacturing lot shown in FIG. 5, test strip #4 can be adjusted bysimply measuring the area INTEG 4 and comparing the area of INTEG 4 tothe area of average test strip INTEG 3. As such, the final reflectancevalue F₄ will be adjusted downwardly (from F₄ to F₃) by an amountproportional to the difference in size between INTEG 4 and INTEG 3according to the calibration equation established for this exemplarymanufacturing lot of test strips.

As understood herein, a lateral flow assay test strip encompasses anyquantitative lateral flow assay system that is based on the capture of asignal generating species as it flows through a detection zone. Inpreferred embodiments, the reflectance values may be measured at alocation on the test strip as a sample with a concentrated front of dyedmicroparticles passes thereover, and wherein the final reflectance valueis measured at the location on the test strip after microparticlecapture and clearing of non-bound microparticles has occurred.Preferably, the signal values are all measured at the same location onthe test strip.

Any of the above final signal values F may be measured a pre-determinedperiod of time after the commencement of the lateral flow assayreaction.

In accordance with the present invention, minimum signal values may beused when analyzing reflectance kinetic profiles. In contrast, maximumsignal values may be used when examining fluorescence kinetic profiles.Therefore, in the present specification and claims, the term “maximum”may be substituted for the term “minimum”. Moreover in the presentspecification and claims, the term “extreme” may be used to includeeither a “maximum” or a “minimum”. As also understood herein, an“exemplary” test strip (i.e.: #3 as illustrated herein) may include acalculated mean, median or average test strip that is representative oftest strips from a particular manufacturing lot.

Also in accordance with the present invention is identifying thepre-determined calibration method used for the manufacturing lot, towhich a particular newly selected test strip belongs, by reading anidentifier that indicates which pre-determined adjustment method is tobe used. For example, a test strip made from the manufacturing lot oftest strips shown in FIG. 1 may carry an identification tag stating thatthe calibration method to be used is that which is illustrated in FIG.1, along with the parameter values uniquely characteristic of that teststrip's manufacturing lot, wherein such an identification tag may bemounted on the test strip itself or on an assembly connected to the teststrip.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

The invention claimed is:
 1. A method of adjusting a final signal valuemeasured on a lateral flow assay test strip, comprising: measuringsignal values, the signal values resulting from optical analysis of atest strip with a meter wherein the meter measures the signal values,while performing a lateral flow assay reaction on the test strip, eachof the signal values representative of an optical property of thelateral flow assay test strip at a point in time, the signal valuesmeasured over a time period during which the lateral flow assay teststrip is tested; determining a minimum signal value using the meter, themeter configured to perform the determining of the minimum signal valueand including instructions that the meter executes, the instructionsstored in a computer readable medium, wherein the minimum signal valueis the minimum measured value of reflectance measurements of the signalvalues; determining the time at which the minimum signal value ismeasured; determining a final signal value, wherein the minimum signalvalue and the final signal value are not the same using the meter, themeter configured to perform the determining of the time and the finalsignal value and including instructions that the meter executes, theinstructions stored in a computer readable medium; and adjusting thefinal signal value using the meter to account for differences in a lotof test strips from which the lateral flow assay test strip originatesas compared to an expected test strip, the lot of test strips from thesame manufacturing lot, the meter configured to perform the adjusting ofthe final signal and including instructions that the meter executes, theinstructions stored in a computer readable medium, based upon the timeat which the minimum signal value is measured compared to an expectedtime at which minimum signal values are reached, wherein the finalsignal value is decreased when the minimum signal value is measuredearly as compared to the expected time.
 2. A method of adjusting a finalsignal value measured on a lateral flow assay test strip, comprising:measuring signal values, the signal values resulting from opticalanalysis of a test strip with a meter wherein the meter measures thesignal values, while performing a lateral flow assay reaction on thetest strip, each of the signal values representative of an opticalproperty of the lateral flow assay test strip at a point in time, thesignal values measured over a time period for testing the test strip;determining a total signal below a threshold value using the meter, themeter configured to perform the determining of the total signal below athreshold value and including instructions that the meter executes, theinstructions stored in a computer readable medium, wherein the totalsignal below the threshold value is based on a total area calculatedbetween a line formed by the signal values and the threshold value;determining a final signal value; and adjusting the final signal valueusing the meter to account for differences in a lot of test strips fromwhich the lateral flow assay test strip originates as compared to anexpected test strip, the lot of test strips from the same manufacturinglot, the meter configured to perform the adjusting of the final signaland including instructions that the meter executes, the instructionsstored in a computer readable medium, based upon comparing the totalmeasured signal below the threshold value, which is a graphed areabetween the threshold value and a curve composed of the signal values,to an expected total measured signal, wherein the final signal value isincreased when the graphed area is less than the expected total measuredsignal.
 3. The method of claim 2, wherein the signal values arereflectance values.
 4. A method of adjusting a final signal valuemeasured on a lateral flow assay test strip, comprising: measuringsignal values, the signal values resulting from optical analysis of atest strip with a meter wherein the meter measures the signal values,while performing a lateral flow assay reaction on the test strip, eachof the signal values representative of an optical property of thelateral flow assay test strip at a point in time, the signal valuesmeasured over a time period during which the lateral flow assay teststrip is tested; determining a minimum signal value using the meter, themeter configured to perform the determining of the minimum signal valueand including instructions that the meter executes, the instructionsstored in a computer readable medium, wherein the minimum signal valueis the minimum measured value of reflectance measurements of the signalvalues; determining the time at which the minimum signal value ismeasured; determining a final signal value, wherein the minimum signalvalue and the final signal value are not the same using the meter, themeter configured to perform the determining of the time and the finalsignal value and including instructions that the meter executes, theinstructions stored in a computer readable medium; and adjusting thefinal signal value using the meter to account for differences in a lotof test strips from which the lateral flow assay test strip originatesas compared to an expected test strip, the lot of test strips from thesame manufacturing lot, the meter configured to perform the adjusting ofthe final signal and including instructions that the meter executes, theinstructions stored in a computer readable medium, based upon the timeat which the minimum signal value is measured compared to an expectedtime at which minimum signal values are reached, wherein the finalsignal value is increased when the minimum signal value is measured lateas compared to the expected time.
 5. The method of claim 1, wherein theamount of decrease of the final signal value is proportional to adifference between the time at which the minimum signal value ismeasured and the expected time.
 6. The method of claim 4, wherein theamount of increase of the final signal value is proportional to adifference between the time at which the minimum signal value ismeasured and the expected time.
 7. A method of adjusting a final signalvalue measured on a lateral flow assay test strip, comprising: measuringsignal values, the signal values resulting from optical analysis of atest strip with a meter wherein the meter measures the signal values,while performing a lateral flow assay reaction on the test strip, eachof the signal values representative of an optical property of thelateral flow assay test strip at a point in time, the signal valuesmeasured over a time period for testing the test strip; determining atotal signal below a threshold value using the meter, the meterconfigured to perform the determining of the total signal below athreshold value and including instructions that the meter executes, theinstructions stored in a computer readable medium, wherein the totalsignal below the threshold value is based on a total area calculatedbetween a line formed by the signal values and the threshold value;determining a final signal value; and adjusting the final signal valueusing the meter to account for differences in a lot of test strips fromwhich the lateral flow assay test strip originates as compared to anexpected test strip, the lot of test strips from the same manufacturinglot, the meter configured to perform the adjusting of the final signaland including instructions that the meter executes, the instructionsstored in a computer readable medium, based upon comparing the totalmeasured signal below the threshold value, which is a graphed areabetween the threshold value and a curve composed of the signal values,to an expected total measured signal, wherein the final signal value isdecreased when the graphed area is greater than the expected totalmeasured signal.